Antiobesity designed multiple ligands: Synthesis of pyrazole fatty acid amides and evaluation as hypophagic agents.
Searching for new antiobesity agents, a new series of fatty acid amide derivatives of 1,5-diarylpyrazole have been synthesized as dual peroxisome proliferator activated receptor alpha (PPARalpha)/cannabinoid receptor ligands. The compounds have been evaluated in vivo and in vitro as PPARalpha activators and as cannabinoids in two tests of the mouse tetrad. In vivo, food intake studies have been performed with all the compounds. No significant cannabinoid activity has been found but some compounds behaved as potent PPARalpha activators. Several compounds showed anorexigenic properties reducing food intake in rats.
Alvarado
Mario
M
Instituto de Química Médica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
Goya
Pilar
P
Macías-González
Manuel
M
Pavón
Francisco Javier
FJ
Serrano
Antonia
A
Jagerovic
Nadine
N
Elguero
Jose
J
Gutiérrez-Rodríguez
Angel
A
García-Granda
Santiago
S
Suardíaz
Margarita
M
Rodríguez de Fonseca
Fernando
F
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002186:Cannabinoids / Q000737:chemistry / Q000378:metabolism; D004435:Eating; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D051379:Mice; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000577:Amides; D019440:Anti-Obesity Agents; D002186:Cannabinoids; D005227:Fatty Acids; D047493:PPAR alpha; D011720:Pyrazoles; D005982:Glutathione Transferase